Overall Project Summary The Washington University Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) initiates, fosters, and supports the performance of innovative, cutting-edge research on Alzheimer disease (AD) and related dementias (ADRD) with regard to the etiology, pathogenesis, diagnosis, treatment, and prevention of disease. The Knight ADRC's efforts thus fully align with the primary goal of the National Alzheimer's Project Act of 2011, ?to prevent and effectively treat ADRD by 2025?. We provide well- characterized research participants (persons with symptomatic AD and age-matched controls), their clinical, psychometric, and imaging data, and their tissue (DNA, CSF, plasma, dermal fibroblasts, iPSCs, brain tissue) to research projects. We also provide intellectual and financial support to scientists at Washington University, at other Alzheimer Disease Centers, and the research community nationally and internationally and engage in formal and informal collaborations, including multi-disciplinary/multi-Center studies and the initiatives sponsored by the National Institute on Aging, the National Alzheimer Coordinating Center, and the National Centralize Repository for ADRD. Historically, our Center has focused on the earliest stages of dementia to identify the initial clinical and pathologic changes that distinguish AD from normal aging. Our approach is balanced between clinical and basic science domains with emphasis on interdisciplinary efforts. We will continue our training of students, fellows and junior faculty in clinical and basic science research skills. We will continue to engage in outreach activities to transfer information on ADRD to lay and professional audiences. We are committed to assuring that our research cohort reflects the racial diversity of the greater metropolitan St. Louis area and will continue activities that promote the inclusion of these populations in research. This renewal application includes seven Cores, plus the new Research Education Component (REC): A: Administration, B: Clinical, C: Data Management and Statistics, D: Neuropathology, E: Outreach, Recruitment, and Engagement, F: Biomarker, G: Genetics and High Throughput -Omics.